Evolutionary, structural and functional insights in nuclear organisation and nucleocytoplasmic transport in trypanosomes

One of the remarkable features of eukaryotes is the nucleus, delimited by the nuclear envelope (NE), a complex structure and home to the nuclear lamina and nuclear pore complex (NPC). For decades, these structures were believed to be mainly architectural elements and, in the case of the NPC, simply facilitating nucleocytoplasmic trafficking. More recently, the critical roles of the lamina, NPC and other NE constituents in genome organisation, maintaining chromosomal domains and regulating gene expression have been recognised. Importantly, mutations in genes encoding lamina and NPC components lead to pathogenesis in humans, while pathogenic protozoa disrupt the progression of normal development and expression of pathogenesis-related genes. Here, we review features of the lamina and NPC across eukaryotes and discuss how these elements are structured in trypanosomes, protozoa of high medical and veterinary importance, highlighting lineage-specific and conserved aspects of nuclear organisation.</p

Evolution and diversification of the nuclear pore complex

The nuclear pore complex (NPC) is responsible for transport between the cytoplasm and nucleoplasm and one of the more intricate structures of eukaryotic cells. Typically composed of over 300 polypeptides, the NPC shares evolutionary origins with endo-membrane and intraflagellar transport system complexes. The modern NPC was fully established by the time of the last eukaryotic common ancestor and, hence, prior to eukaryote diversification. Despite the complexity, the NPC structure is surprisingly flexible with considerable variation between lineages. Here, we review diversification of the NPC in major taxa in view of recent advances in genomic and structural characterisation of plant, protist and nucleomorph NPCs and discuss the implications for NPC evolution. Furthermore, we highlight these changes in the context of mRNA export and consider how this process may have influenced NPC diversity. We reveal the NPC as a platform for continual evolution and adaptation

Prospectus, May 13, 1974

CLASS OF \u2774 COMMENCEMENT; Openhouse Set For May 19; 648 Parkland Students Eligible To Participate; Dr. Winters To Speak At Graduation; Parkland Groups Win Awards At Jazz Fest; StuGo President Offers Welcome; Dental Students Capped At Banquet; The Short Circuit; Letters To The Editor; New Stu-Go Officer; President\u27s Report; Crosswords; Parkland College Student Life; Instructional Programs; Admission: Who may Enroll?; Tuition & Fees; Financial Aid; Counseling; Placement; Veterans; Student Life; Summer Session 1974; Academic Calendar 1974-1975; Semester System Fall 1975; In Campus Design, Parkland: Not Just Another School; No Golden Quill This Quarter; Petitioned and Qualified Candidates Spring Quarter 1973-1974; One-Punch Leads To Death Of UI Student; Movie Projector Reported Missing; A Column By and For Women; A Column By and For Men; Self-Help Clinic Set For Women; Vet\u27s Corner; Field Trip Meeting Set; Pig Guards Pot Plot From Police Raid; Blood Drive; Summer Field Course In American Southwest; P/C Student Wins Distinguished Award; Allerton Day Shows Ecological Benefits Of Park; Debate Team Finishes Best Year Ever; Monday\u27s Coach; Thank You; High-Scoring Henrichs Opts For Parkland Cage Team; Parkland Coaches Review Year; Cobras Bat Way Over .500; P/C Players Thrill Audience; Bartow On His Way; Pritchett Not To Be Outdone; On The Way Out; Classified Ads; End-Of-Year Gala Planned By Phys Ed. Dept.; Social, Religious Traditions Expressed In Roots Afrikana; Jones Cites Improvements In Prospectus; Prospectus Staff Positions Open For New School Year; Business Student Wins Award; Krannert Art Schedule; Many Financial Awards Open To Incoming Parkland Students; Parkland Vets Info Center On Wheelshttps://spark.parkland.edu/prospectus_1974/1012/thumbnail.jp

Identification and Validation of Compounds Targeting Leishmania major Leucyl-Aminopeptidase M17

Leishmaniasis is a neglected tropical disease; there is currently no vaccine and treatment is reliant upon a handful of drugs suffering from multiple issues including toxicity and resistance. There is a critical need for development of new fit-for-purpose therapeutics, with reduced toxicity and targeting new mechanisms to overcome resistance. One enzyme meriting investigation as a potential drug target in Leishmania is M17 leucyl-aminopeptidase (LAP). Here, we aimed to chemically validate LAP as a drug target in L. major through identification of potent and selective inhibitors. Using RapidFire mass spectrometry, the compounds DDD00057570 and DDD00097924 were identified as selective inhibitors of recombinant Leishmania major LAP activity. Both compounds inhibited in vitro growth of L. major and L. donovani intracellular amastigotes, and overexpression of LmLAP in L. major led to reduced susceptibility to DDD00057570 and DDD00097924, suggesting that these compounds specifically target LmLAP. Thermal proteome profiling revealed that these inhibitors thermally stabilized two M17 LAPs, indicating that these compounds selectively bind to enzymes of this class. Additionally, the selectivity of the inhibitors to act on LmLAP and not against the human ortholog was demonstrated, despite the high sequence similarities LAPs of this family share. Collectively, these data confirm LmLAP as a promising therapeutic target for Leishmania spp. that can be selectively inhibited by drug-like small molecules.</p

Prospectus, November 9, 1973

FORD - OUR NEXT PRESIDENT?; Faculty, Staff Evaluations Adopted As College Policy; Fellowships For Women Announced; Student Senate Vice-President Resigns Post; Debaters Take Third At IVC Meet; Vandalism Suspected In Fire; Parkland To Participate In Conference; Declaration Of Impeachment; Prospectus In Perspective; Letters From Our Readers; Student Opinion Survey; President\u27s Comment; The Short Circuit; Behind The Books; Counselors And Question Marks; Zindars Shares Her Experiences; $6 Bid Tops In Vets Dance, Slave-Auction; UFO\u27s: Citizens Vs. Air Force; The Pinkertons Are At Parkland; Allied Health Program; November Student Activities Parkland College; American Assoc. Of Univ. Women Host General Meeting Nov. 11; Peterson Addresses Phi Beta Lambda; PLATO Popular With Students, Teachers; Cycle Mishap Injures One; Road Rally; Mutt and Mortie; Evening Program Diversified Next Quarter At P/C; Geology Flight Delayed; Final Exam Schedule - Fall Quarter; Costs At School Dominate P.C.A. Senate Meeting; \u27Passion Play\u27 Not Dull; P/C Gen. Biology-Pollution, Genetics Other Relevant Topics; No Grease-Monkey Graduatess At Parkland; Campus Leaders Exchange Ideas at Allerton Meeting; Parkland Co-Hosts Veterans Conference; TB Examinations; Classified Ads; A Column By And For Women: Originality, The Cell; Monday\u27s Coach; Jim Redman, Jane Hawthorne Grab Parkland\u27s First Road Rally; Football Finals To Be Held Tuesday; Fast Freddy\u27s Football Forecast; WVLJ Plans Broadcasts Of PC Basketball; Thompson Wins Fast Freddy As Upsets Abound; Local Volunteer Suggests Grants; Lost And Found; Earle, Seger Go To N.J.C.A.A. Nationals; Parkland Cagers Start Practice For Nov. 29 Debut With Millikin; Wrestlers Open Workouts, Seven Spots Open On 10-Man Roster; Parkland College Basketball Schedule 1973-74; Parkland College Wrestling Schedule 1973-74; Bowing Bulletin Board; Callboard; Changes In Calendar, Staff Status, Registration Proposed; Cade Re-elected Board Chairmanhttps://spark.parkland.edu/prospectus_1973/1002/thumbnail.jp

Diagnosis and Management of Cerebral Venous Thrombosis: A Scientific Statement From the American Heart Association

Cerebral venous thrombosis accounts for 0.5% to 3% of all strokes. The most vulnerable populations include young individuals, women of reproductive age, and patients with a prothrombotic state. The clinical presentation of cerebral venous thrombosis is diverse (eg, headaches, seizures), requiring a high level of clinical suspicion. Its diagnosis is based primarily on magnetic resonance imaging/magnetic resonance venography or computed tomography/computed tomographic venography. The clinical course of cerebral venous thrombosis may be difficult to predict. Death or dependence occurs in 10% to 15% of patients despite intensive medical treatment. This scientific statement provides an update of the 2011 American Heart Association scientific statement for the diagnosis and management of cerebral venous thrombosis. Our focus is on advances in the diagnosis and management decisions of patients with suspected cerebral venous thrombosis. We discuss evidence for the use of anticoagulation and endovascular therapies and considerations for craniectomy. We also provide an algorithm to optimize the management of patients with cerebral venous thrombosis and those with progressive neurological deterioration or thrombus propagation despite maximal medical therapy

What Works for Wellbeing? A systematic review of wellbeing outcomes for music and singing in adults

IMS: The role of arts and music in supporting subjective wellbeing (SWB) is increasingly recognised. Robust evidence is needed to support policy and practice. This article reports on the first of four reviews of Culture, Sport and Wellbeing (CSW) commissioned by the Economic and Social Research Council (ESRC)-funded What Works Centre for Wellbeing ( https://whatworkswellbeing.org/ ). OBJECTIVE: To identify SWB outcomes for music and singing in adults. METHODS: Comprehensive literature searches were conducted in PsychInfo, Medline, ERIC, Arts and Humanities, Social Science and Science Citation Indexes, Scopus, PILOTS and CINAHL databases. From 5,397 records identified, 61 relevant records were assessed using GRADE and CERQual schema. RESULTS: A wide range of wellbeing measures was used, with no consistency in how SWB was measured across the studies. A wide range of activities was reported, most commonly music listening and regular group singing. Music has been associated with reduced anxiety in young adults, enhanced mood and purpose in adults and mental wellbeing, quality of life, self-awareness and coping in people with diagnosed health conditions. Music and singing have been shown to be effective in enhancing morale and reducing risk of depression in older people. Few studies address SWB in people with dementia. While there are a few studies of music with marginalised communities, participants in community choirs tend to be female, white and relatively well educated. Research challenges include recruiting participants with baseline wellbeing scores that are low enough to record any significant or noteworthy change following a music or singing intervention. CONCLUSIONS: There is reliable evidence for positive effects of music and singing on wellbeing in adults. There remains a need for research with sub-groups who are at greater risk of lower levels of wellbeing, and on the processes by which wellbeing outcomes are, or are not, achieved